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An assessment of triclosan susceptibility in methicillin-resistant and methicillin-sensitive Staphylococcus aureus.

Triclosan is widely used to reduce skin colonization with staphylococci and is incorporated into methicillin-resistant Staphylococcus aureus (MRSA) eradication regimes. Using an agar dilution method, the minimum inhibitory concentration (MIC) to triclosan was determined for 186 isolates of MRSA and methicillin sensitive Staphylococcus aureus (MSSA). Fourteen isolates (7.5%) were detected with a MIC > or = 1.0 part per million (ppm). There was no significant difference between the incidence of triclosan resistance in strains of MSSA and MRSA. None of 16 strains of MRSA which exhibited low-level mupirocin resistance had MIC's > or = 1.0 ppm. Increased MIC's of staphylococci to triclosan may contribute to treatment failure when used to eradicate staphylococcal carriage. We suggest that routine susceptibility testing of staphylococci against triclosan might now be indicated.

Anti-Infective Agents, Local↗

Comparison of methicillin-resistant and methicillin-sensitive Staphylococcus aureus bacteremia.

Methicillin-resistant Staphylococcus aureus (MRSA) has become endemic in Detroit, accounting for 50% of bacteremias in heroin abusers. To identify the salient epidemiologic and clinical features of MRSA bacteremia, case-control studies were performed comparing 28 cases of MRSA bacteremia to 28 cases of methicillin-sensitive S. aureus (MSSA) bacteremia in intravenous drug abusers. Infective endocarditis was diagnosed in 46.4% (13 of 28). In endocarditis and nonendocarditis bacteremia alike, the duration of fever, length of hospitalization, need for surgery, and mortality rates were similar. A history of recent antimicrobial therapy, especially cephalosporins, was more common in the MRSA group (p = 0.006). Complications including neurologic, renal, vascular, and musculoskeletal manifestations were more common in the MSSA endocarditis patients than MRSA endocarditis patients, although this difference was not significant. Complications related to antibiotic therapy were similar for both groups. The case-control studies indicate that MRSA and MSSA are similar in their virulence as measured by duration of hospitalization, duration of fever, complications, and mortality.

Endocarditis↗

Characterization of methicillin-susceptible and methicillin-resistant Staphylococcus aureus isolates by molecular typing methods.

Two groups of clinical Staphylococcus aureus isolates were examined by molecular typing methods. Detailed protocols for the technical procedures are described. By means of plasmid DNA profiles, plasmid DNA restriction enzyme digestion, as well as whole-cell DNA endonuclease digestions subjected to conventional agarose gel electrophoresis and pulsed-field gel electrophoresis, eight methicillin-susceptible S. aureus strains from three patients segregated into three different groups. Consecutive isolates from the same patient revealed identical fingerprints. Generally, good agreement between different molecular typing methods also was achieved in the investigation of 28 methicillin-resistant isolates. However, compared to whole-cell DNA restriction endonuclease analysis, plasmid DNA profiling (all but one strain had detectable plasmid DNA) showed a somewhat greater discriminatory ability. The techniques evaluated were reproducible and relatively easy to perform and provided valuable tools for studying the epidemiology of S. aureus in hospitals.

Bacterial Typing Techniques↗

A comparison of pneumonia caused by gentamicin, methicillin-resistant and gentamicin, methicillin-sensitive Staphylococcus aureus: epidemiologic and clinical studies.

We investigated an outbreak of nosocomial pneumonia due to gentamicin, methicillin-resistant Staphylococcus aureus (GMRSA). We compared the predisposing factors for pneumonia due to GMRSA to those for pneumonia due to gentamicin, methicillin-sensitive Staphylococcus aureus (GMSSA). Seventeen of 29 patients with staphylococcal pneumonia were infected with GMRSA. Risk factors and associated diseases which selected for infection with GMRSA as opposed to GMSSA included prior antibiotic therapy for a prolonged period of time (p = 0.0001), number of risk factors per patient (p = 0.0001), days hospitalized prior to diagnosis of pneumonia (p = 0.002) and number of associated diseases per patient (p = 0.002). Despite the epidemiologic differences between GMSSA and GMRSA pneumonia, there were no differences in the clinical presentation, course of illness, complications, response to appropriate therapy or outcome between the two groups. Survival was adversely affected by age only among the GMSSA patients (p = 0.02) and by the number of associated diseases (p = 0.005).

Anti-Bacterial Agents↗

Hospital-acquired infection with methicillin-resistant and methicillin-sensitive staphylococci.

In-patients at a London hospital over one year from whom the south-east England strain of 'epidemic' methicillin-resistant Staphylococcus aureus (MRSA) was isolated were compared with in-patients with strains of methicillin-sensitive Staphylococcus aureus (MSSA). MRSA were virtually entirely hospital-acquired; isolates before 10 days were uncommon and related to recent previous admission. Thereafter first isolates occurred at a fairly constant daily rate of about 1.9 per 1,000 in-patients. Acquisition of MSSA after more than 4 days in hospital occurred at a similar constant rate. Such strains were less likely to be penicillin-sensitive than strains isolated in the first 4 days after admission (11 vs. 22%) and were considered to be hospital-acquired. The single MRSA strain caused 40 infections in a year, about half of all hospital-acquired staphylococcal infections. Patients prescribed anti-staphylococcal antibiotics and patients with indwelling cannulae both had about a ninefold increased risk of acquiring MRSA. There was no reciprocal increase in MSSA infections after control measures had substantially reduced the number of MRSA infections.

Cross Infection↗

The impact of nasal carriage of methicillin-resistant and methicillin-susceptible Staphylococcus a ureus (MRSA & MSSA) on vascular access-related septicemia among patients with type-II diabetes on dialysis.

BACKGROUND: Fairly higher nasal carriage rates among type-II diabetics place them at a greater risk of endogenous Staphylococcus aureus linked vascular access-related septicemia (VRS) that is also dependent on the type of vascular access used for hemodialysis (HD). The prevalence of nasal carriage of methicillin susceptible and methicillin-resistant S. aureus (MSSA and MRSA) and its impact on VRS was determined in order to identify most vulnerable group and plan potential prophylactic strategies, accordingly. METHODS: Five standardized nasal swab cultures were performed in 208 patients enrolled for long-term HD through July 1996 to July 1999. Persistent nasal carriage was defined by two or more positive cultures for MSSA or MRSA. Peripheral blood cultures were collected on clinical suspicion of septicemia. RESULTS: The prevalence of type-II diabetes of 28.0% with 72.4% of nasal carriage rate and three folds higher S. aureus related VRS (RR-3.19, p<0.0001) than diabetic non-carriers on HD, was observed. Type-II diabetics also had higher MSSA and MRSA nasal carriage rates (53.4% and 19.0%) than non-diabetic nasal carriers (18.6 and 6.0%) yet, carried a comparable (RR-4.0 vs. 4.5) risk of VRS between MSSA and MRSA nasal carriers. Among diabetic type-II S. aureus nasal carriers, central venous catheters (CVCs) carried 35 and 38 times higher collective risk of developing MSSA and MRSA nasal carriage-related VRS respectively than Arterio-venous fistula (AVF). The AVF recorded the lowest risk of developing MSSA and MRSA nasal carriage-related VRS (0.013 and 0.010 episodes/patient-year) in both diabetic type-II MSSA and MRSA nasal carrier groups. CONCLUSIONS: Diabetic type-II S. aureus nasal carriers on HD through CVCs make an extremely high-risk group for MSSA and MRSA nasal carriage-related VRS. The incidence of S. aureus nasal carriage-related VRS could reasonably be reduced through a challenging obligation of optimizing AVF prevalence in this high-risk group, while limiting the use of CVCs, at the same time.

Adolescent↗

Prevalence of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in the community.

Recent reports indicate that community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing and may now involve persons without risk factors predisposing for acquisition. To estimate the extent of community MRSA in New York City, the prevalence of S. aureus and MRSA nasal colonization in a well-patient population of 500 children and guardians was determined. The prevalence of S. aureus nasal carriage was 35% for children and 28% for guardians. One person with predisposing risk factors was colonized with an MRSA, which was identified as the predominant clone found in New York City hospitals. A high degree of methicillin-susceptible S. aureus strain diversity was noted, with no apparent selection for specific clonal types. Thus, MRSA colonization is not ubiquitous in persons without predisposing risk outside of the health care environment. Bacterial competition and a lack of strong selection may limit the community spread of MRSA and can account for its sporadic distribution.

Adolescent↗

Poststernotomy mediastinitis due to Staphylococcus aureus: comparison of methicillin-resistant and methicillin-susceptible cases.

The objective of the study was to compare the outcome of poststernotomy mediastinitis (PSM) caused by methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA, respectively). Hospital records of 41 patients with S. aureus PSM who were all treated by closed drainage from 1 April 1996 through 1 February 2000 were reviewed. PSM was caused by MRSA in 15 patients and by MSSA in 26. Follow-up (+/-SD) averaged 12.5+/-14.0 months per patient. Both groups had similar perioperative characteristics. Patients with MRSA PSM had a significantly lower actuarial survival rate than did patients with MSSA PSM (60.0%+/-12.6%, 52.5%+/-3.4%, and 26.3%+/-19.7% versus 84.6%+/-7.1%, 79.0%+/-8.6%, and 79.0%+/-8.65 at 1 month, and at 1 and 3 years, respectively; values are +/- SD; P=.04). PSM-related death and treatment failure were significantly higher in the MRSA group than in the MSSA group (P=.03 and.02, respectively). Logistic regression analysis revealed that MRSA was the only independent risk factor for overall mortality. In conclusion, the clinical outcome of PSM caused by MRSA is poorer than that caused by MSSA.

Adult↗

Nosocomial methicillin-resistant Staphylococcus aureus bacteremia: is it any worse than nosocomial methicillin-sensitive Staphylococcus aureus bacteremia?

OBJECTIVE: To determine the comparative virulence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S aureus (MSSA) by consideration of predisposing factors and outcomes in patients infected with these organisms in the healthcare setting. DESIGN: Analysis of an historical cohort of 504 bacteremic patients (316 MSSA and 188 MRSA), examining factors associated with mortality. SETTING: A 916-bed, university-affiliated, tertiary referral hospital. RESULTS: Risk factors for the development of MRSA include male gender, admission due to trauma, immunosuppression, presence of a central vascular line or an indwelling urinary catheter, and a past history of MRSA infection. Overall mortality was 22%. Death due to bacteremia was significantly greater in the MRSA group (risk ratio, 1.68; P<.05), although these patients were not found to be more likely to die due to underlying disease during treatment of bacteremia. In those patients who recovered from bacteremia, no significant differences for the outcome of death could be determined between the MRSA and MSSA groups. CONCLUSIONS: There is a general consensus in the published literature that MRSA bacteremia is more likely to be associated with death, and we confirm this conclusion. However, in contrast to other studies, our MRSA cohort does not appear to be more at risk of death due to underlying disease during treatment for bacteremia. Similarly, the general consensus that MRSA patients have an increased overall mortality was not confirmed in our study. Differences in comorbidities of patients may provide some explanation of these conflicting results, while an alternate explanation is that MRSA strains are more virulent than MSSA in some centers. Perhaps the most plausible explanation is that treatment is provided earlier and in a more aggressive fashion in some centers, leading to an overall lower mortality rate in all staphylococcal bacteremias in these institutions.

Australia↗

Rates of carriage of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in an outpatient population.

OBJECTIVES: To assess the prevalence of and the clinical features associated with asymptomatic Staphylococcus aureus colonization in a healthy outpatient population, and to compare the characteristics of colonizing methicillin-resistant S. aureus (MRSA) strains with those of strains causing infection in our community and hospital. SETTING: Outpatient military clinics. METHODS: Specimens were obtained from the nares, pharynx, and axillae of 404 outpatients, and a questionnaire was administered to obtain demographic and risk factor information. MRSA strains were typed by pulsed-field gel electrophoresis (PFGE) and evaluated for antibiotic susceptibility. Antibiograms of study MRSA strains were compared with those of MRSA strains causing clinical illness during the same time period. RESULTS: Methicillin-susceptible S. aureus (MSSA) colonization was present in 153 (38%) of the 404 asymptomatic outpatients, and MRSA colonization was present in 8 (2%). Detection of colonization was highest from the nares. No clinical risk factor was significantly associated with MRSA colonization; however, a tendency was noted for MRSA to be more common in men and in those who were older or who had been recently hospitalized. All colonizing MRSA strains had unique patterns on PFGE. In contrast to strains responsible for hospital infections, most colonizing isolates of MRSA were susceptible to oral antibiotics. CONCLUSIONS: MRSA and MSSA colonization is common in our outpatient population. Colonization is best detected by nares cultures and most carriers of MRSA are without apparent predisposing risk factors for acquisition. Colonizing isolates of MRSA are heterogeneous and, unlike nosocomial isolates, often retain susceptibility to other non-beta-lactam antibiotics.

Adolescent↗

Epidemiology and clonality of methicillin-resistant and methicillin-susceptible Staphylococcus aureus causing bacteremia in a tertiary-care hospital in Spain.

OBJECTIVES: To describe the relative proportions of nosocomial and community-onset Staphylococcus aureus bacteremia at our institution and the epidemiologic characteristics and clonal diversity of S. aureus isolates, as determined by pulsed-field gel electrophoresis (PFGE) and antimicrobial resistance patterns. DESIGN: Retrospective cohort study of all cases of S. aureus bacteremia between October 2001 and October 2002. SETTING: A 1300-bed, tertiary-care hospital. RESULTS: One hundred sixty-two unique episodes of S. aureus bacteremia were identified. Forty-three cases (26.5%) were caused by methicillin-resistant S. aureus (MRSA). Most cases of S. aureus bacteremia, whether MRSA or methicillin susceptible (MSSA), were nosocomial in origin (77.2%) or were otherwise associated with the healthcare system (16%). Only 11 (6.8%) of the cases (all MSSA) were strictly community acquired. Thirty-five unique macrorestriction patterns were identified among the 154 isolates that were typed by PFGE. Four major genotypes were defined among the isolates of MRSA, with 36 (85.7%) represented by a single PFGE type. Of the isolates within this major clone, all (100%) were ciprofloxacin resistant and 77.8% were erythromycin resistant. In contrast, the 112 isolates of MSSA comprised 31 different PFGE types, 3 of which represented 42.9% of all MSSA isolates and were associated with both nosocomial and community-onset bacteremia. CONCLUSIONS: Most cases of S. aureus bacteremia in our healthcare region are nosocomial in origin or are acquired through contact with the healthcare system and are thus potentially preventable. To preclude dissemination of pathogenic clones, it is therefore necessary to redouble preventive measures in both the hospital and the community.

Child, Preschool↗

Inactivation of cefazolin, cephaloridine, and cephalothin by methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus.

Cefazolin was more susceptible than cephaloridine and cephalothin to in vitro inactivation by coagulase-positive, penicillinase-producing strains of Staphylococcus aureus. Inactivation (which was greater with methicillin-resistant than with methicillin-sensitive strains) was demonstrated by assay of the antibiotics in broth cultures with simultaneous colony counts and by exposure of the antibiotics to penicillinase powders extracted from S. aureus. Cefazolin was destroyed to a greater extent than was cephaloridine, whereas cephalothin underwent little, if any, destruction. The clinical implications of this degradation, thought by some to be of importance for cephaloridine, might also apply to cefazolin.

Cefazolin↗

Methicillin-resistant and borderline methicillin-resistant asymptomatic Staphylococcus aureus colonization in children without identifiable risk factors.

BACKGROUND: The recent evolution in the epidemiology of methicillin-resistant asymptomatic Staphylococcus aureus (MRSA) infections in children, whereby children without traditional risk factors for MRSA have been hospitalized in increasing numbers, prompted us to establish whether a parallel increase in "asymptomatic" MRSA colonization had occurred. METHODS: We cultured the nares and perineum of 500 children attending our Pediatric Emergency Department. RESULTS: One hundred thirty-two (26.4%) of these children were colonized with S. aureus. Eleven (8.3%) of the S. aureus isolates were MRSA; 4 (36.4%) of the 11 subjects colonized with MRSA had no risk factors. Seven (5.3%) of the 132 S. aureus isolates were borderline methicillin-resistant S. aureus (BRSA); 5 (71.4%) of the 7 subjects colonized with BRSA had no MRSA risk factors. CONCLUSIONS: These findings indicate that MRSA and BRSA isolates are circulating in the community and that MRSA isolates are no longer confined to children with frequent contact with a health care environment.

Adolescent↗

Community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus musculoskeletal infections in children.

BACKGROUND: The clinical characteristics and virulence factors related to musculoskeletal infections caused by community-acquired, methicillin-resistant Staphylococcus aureus (MRSA) in children are not well-defined. METHODS: In this retrospective study, the demographics, hospital course and outcome of children with musculoskeletal infections were reviewed from medical records and by contacting patients or their physicians. Antimicrobial susceptibilities were determined by disk diffusion. Polymerase chain reaction was performed to detect genes encoding for virulence factors. Mann-Whitney, chi2 and Kaplan-Meier tests were used for statistical analysis. RESULTS: Community-acquired MRSA and community-acquired methicillin-susceptible S. aureus (MSSA) caused musculoskeletal infections in 31 and 28 children, respectively. The median numbers of febrile days after start of therapy were 4 and 1 for MRSA and MSSA patients, respectively (P = 0.001). The median numbers of hospital days were 13 and 8 for the MRSA and MSSA groups, respectively (P = 0.014). At follow-up, 2 patients in the MRSA and 1 in the MSSA group had developed chronic osteomyelitis. pvl and fnbB genes were found in 87 and 90% versus 24 and 64% in the MRSA versus MSSA groups, respectively. (P = 0.00001 and 0.017). Ten patients with pvl-positive strains had complications versus no patients with pvl-negative isolates (P = 0.002). CONCLUSIONS: Febrile days and hospital days were greater in children with musculoskeletal infection caused by MRSA than in those affected by MSSA, but no significant differences were found in the final outcome. pvl and fnbB genes were more frequent in the MRSA than in the MSSA strains. The presence of the pvl gene may be related to an increased likelihood of complications in children with S. aureus musculoskeletal infections.

Adolescent↗

Plasmid profiles and restriction enzyme fragmentation patterns of plasmids of methicillin-sensitive and methicillin-resistant isolates of Staphylococcus aureus from hospital and the community.

The number, frequency distribution and restriction enzyme fragmentation patterns of plasmids harboured by 163 methicillin-sensitive isolates of Staphylococcus aureus (MSSA) and 53 methicillin-resistant isolates (MRSA) were compared. Plasmids were demonstrated in less than half of the MSSA isolates; their frequency distribution did not differ from that predicted by a simple model of plasmid distributions. In contrast, all the MRSA isolates harboured plasmids, their distribution suggesting dissemination of a limited number of clones within the hospital. Among 72 MSSA isolates harbouring plasmids, 38 different restriction patterns were identified. There were fewer patterns among MRSA isolates; 11 were observed, and two predominant patterns accounted for 68% of those identified. These restriction patterns correlated with the presence or absence of aminoglycoside resistance. A multicopy plasmid of 2.6 kb was present in both MSSA and MRSA isolates that harboured more than one plasmid; it had the same restriction pattern irrespective of its source. The importance of these results in choosing a method of studying the spread of staphylococci is discussed.

Cross Infection↗

Adherence and survival properties of an epidemic methicillin-resistant strain of Staphylococcus aureus compared with those of methicillin-sensitive strains.

The adherence of epidemic methicillin-resistant Staphylococcus aureus-1 (EMRSA-1) to HEp2 cells and fibronectin and its survival on formica blocks were compared with the equivalent properties of methicillin-sensitive strains of S. aureus. EMRSA-1 bound to HEp2 cells and fibronectin significantly less than the other strains of S. aureus tested, but survival on formica blocks was similar for all strains except the 'Oxford' S. aureus, which survived poorly.

Bacterial Adhesion↗

Methicillin potentiates the effect of gentamicin on methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) strains show an unusual type of resistance at 37 degrees C; only a small subpopulation of cells is resistant to the beta-lactam antibiotics. Incubation in the presence of methicillin (MET), however, results in the emergence of a homogenous population highly resistant to MET. The purpose of the present study was to determine whether MET, despite its lack of killing effect on MRSA, would promote the bactericidal effect of gentamicin (GM), as demonstrated for MET-susceptible strains of S. aureus. Eleven epidemiologically distinct strains of MRSA were incubated with MET at various concentrations, in the presence or absence of sub-bactericidal concentrations (1/5 or 1/10 of the minimal bactericidal concentration) of GM, and tested for the synergistic action of both antibiotics by three different methods. Population analysis of the 11 strains in the presence of high concentrations of MET showed that the addition of GM at 1/5 or 1/10 of its minimal bactericidal concentration resulted in marked killing of the 11 strains. Time-kill curves obtained with 32 mug of MET per ml and GM at 1/5 or 1/10 of its minimal bactericidal concentration confirmed this synergistic killing at 24 h. These results were further documented by the checkerboard method on two strains. We conclude that the synergism between MET and GM, previously demonstrated for MET-susceptible S. aureus, holds true for MRSA as well and that it can be demonstrated at sub-bactericidal concentrations of GM.

Drug Synergism↗

Imipenem-cilastatin in the treatment of methicillin-sensitive and methicillin-resistant Staphylococcus aureus infections.

Imipenem-cilastatin was evaluated for efficacy and toxicity as an antistaphylococcal agent in 23 patients; 11 of these patients were infected with methicillin-resistant Staphylococcus aureus (MRSA), and 12 were infected with methicillin-susceptible S. aureus (MSSA). There were 15 soft tissue, 5 endovascular, and 3 skeletal infections and a total of nine patients with bacteremia. As determined by in vitro susceptibility testing, the MICs for 90% of the MRSA and MSSA isolates tested were 6.25 and 0.39 micrograms/ml, respectively. Two MRSA isolates were resistant to a concentration of greater than 16 micrograms/ml. When 11 MRSA isolates and 7 MSSA isolates were incubated for 48 h the MICs for 90% of the isolates increased to greater than 50 micrograms/ml for the MRSA isolates and 6.25 micrograms/ml for the MSSA isolates. Three S. aureus isolates emerged resistant. Ten of 11 (91%) MRSA infections and 11 of 12 (92%) MSSA infections were clinically cured. Adverse reactions occurred in 25% of the imipenemcilastatin-treated patients. These reactions included gastrointestinal intolerance (7% of the patients), rash or pruritus (6%), eosinophilia (6%), thrombocytosis (4%), and a positive, direct Coomb test without hemolysis (3%). One of the two patients for whom therapy was discontinued because of gastrointestinal intolerance had antibiotic-associated colitis. Imipenem appears to be an effective antistaphylococcal agent against both MRSA and MSSA infections.

Adult↗